Triethylamine → 5-(Cyclopropylmethoxy)-2-[(trimethylsilyl)ethynyl]pyridine

HRID 1026314Notes

Reaction equation

HRID 1026314 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[CH:4][N:3]=1.[CH3:13][Si:14]([C:17]#[CH:18])([CH3:16])[CH3:15].C(N(CC)CC)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C=O)C>[CH:10]1([CH2:9][O:8][C:5]2[CH:6]=[CH:7][C:2]([C:18]#[C:17][Si:14]([CH3:16])([CH3:15])[CH3:13])=[N:3][CH:4]=2)[CH2:12][CH2:11]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 578217962-Bromo-5-(cyclopropylmethoxy)pyridine

Product 1

HCID 677778225-(Cyclopropylmethoxy)-2-[(trimethylsilyl)ethynyl]pyridineYield 62.8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-bromo-5-(cyclopropylmethoxy)pyridine (1.145 g), bis(triphenylphosphine)palladium(II) dichloride (175 mg), copper(I) iodide (48 mg), trimethylsilylacetylene (737 mg), triethylamine (759 mg) and DMF (15 mL) was stirred at room temperature overnight under an argon atmosphere. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate and water, and the mixture was filtered through celite. The aqueous layer was separated from the organic layer. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as a yellow oil (774 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with ethyl acetate and water
  3. filtrationthe mixture was filtered through celite
  4. customThe aqueous layer was separated from the organic layer
  5. extractionThe separated aqueous layer was extracted again with ethyl acetate
  6. washThe combined organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-b0077d60467344229e3286c41973964e
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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